Functional hypothalamic amenorrhoea and polycystic ovarian morphology: a narrative review about an intriguing association.

IF 14.8 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Human Reproduction Update Pub Date : 2024-10-08 DOI:10.1093/humupd/dmae030
Johannes Ott, Geoffroy Robin, Marlene Hager, Didier Dewailly
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引用次数: 0

Abstract

Background: Functional hypothalamic amenorrhoea (FHA) is responsible for 20-35% of all cases of secondary amenorrhoea and, thus, is the second most common cause of secondary amenorrhoea after polycystic ovary syndrome (PCOS). A high number of patients with FHA reveal polycystic ovarian morphology (PCOM) on ultrasound. The combination of amenorrhoea and PCOM can lead to confusion. First, amenorrhoeic women with PCOM fulfil the revised Rotterdam criteria and, thus, can easily be misdiagnosed with PCOS. Moreover, it has been claimed that some women with FHA and concomitant PCOM differ from those without PCOM in terms of endocrine regulation and metabolic traits.

Objective and rationale: The main focus of this article was on studies about FHA, which differentiated between patients with or without PCOM. The aim was to estimate the prevalence of PCOM and to look if it has an impact on pathophysiologic, diagnostic and therapeutic issues as well as on long-term consequences.

Search methods: Peer review original and review articles were selected from PubMed searches for this review. Searches were performed using the search terms 'polycystic AND functional hypothalamic amenorrhoea'. The reference lists of publications found were searched for relevant additional studies. The inclusion criteria for publications were: English language, patients' age ≥ 18 years, year of publication >1980, original studies, validated diagnosis of FHA, and validated diagnosis of PCOM using transvaginal ultrasound.

Outcomes: The prevalence of PCOM in women with FHA varied from 41.9% to 46.7%, which is higher than in healthy non-PCOS controls. Hypothetically, the high prevalence might be due to a mixture of silent PCOM, as in the general population, and pre-existing PCOS. Several differences in metabolic and hormonal parameters were found between FHA-PCOM and FHA-non-PCOM patients. While oestrogen deficiency is common to both groups of patients, FHA-PCOM patients have a higher BMI, higher levels of anti-Müllerian hormone (AMH) and testosterone, a higher increase in LH in the course of a GnRH test, and lower sex hormone binding globulin (SHBG) levels than FHA-non-PCOM patients. The differential diagnosis between FHA-PCOM and PCOS, especially PCOS phenotype D (PCOM and oligo-/anovulation without hyperandrogenism), can be challenging. Several parameters have been suggested, which are helpful though not absolutely reliable. They include the typical causes for FHA (excessive exercise, energy deficit, and/or psychological stress), the serum levels of LH, testosterone, and SHBG, as well as the progestin challenge test. Whether FHA-PCOM has a different risk profile for long-term consequences concerning patients' metabolic and cardiovascular situation as well as their bone mass, is unclear. Concerning therapeutic aspects, there are only few data about FHA-PCOM compared to FHA-non-PCOM. To treat anovulation, the use of pulsatile GnRH treatment seems to be equally effective in both groups. Similar to FHA-non-PCOM patients, pulsatile GnRH therapy would be more efficient than exogenous gonadotropins in FHA-PCOM patients.

Wider implications: Women with FHA-PCOM present a special sub-population of FHA patients. The diagnostic pitfall of FHA-PCOM should be emphasized in clinical guidelines about FHA and PCOS. The fact that almost half of the women with FHA have an ovarian follicle excess (i.e. PCOM) in face of low gonadotropin serum levels suggests that the intra-ovarian regulation of folliculogenesis is subject to individual variations, for unknown reasons, either genetic or epigenetic. Further studies are needed to investigate this hypothesis.

Registration number: Not applicable.

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功能性下丘脑闭经与多囊卵巢形态:关于一种有趣关联的叙述性综述。
背景:功能性下丘脑性闭经(FHA)占所有继发性闭经病例的 20-35%,因此是继多囊卵巢综合征(PCOS)之后导致继发性闭经的第二大常见原因。大量 FHA 患者在超声检查中发现多囊卵巢形态(PCOM)。闭经和多囊卵巢综合征的结合可能会导致混淆。首先,伴有 PCOM 的闭经妇女符合修订后的鹿特丹标准,因此很容易被误诊为多囊卵巢综合症。此外,有人声称,一些患有 FHA 并伴有 PCOM 的女性在内分泌调节和代谢特征方面与没有 PCOM 的女性有所不同。目的和依据:本文主要关注有关 FHA 的研究,这些研究区分了有无 PCOM 的患者。目的是估算 PCOM 的患病率,并研究 PCOM 是否会对病理生理、诊断和治疗问题以及长期后果产生影响:本综述从 PubMed 搜索中选取了同行评议的原创文章和综述文章。检索词为 "多囊性和功能性下丘脑性闭经"。此外,还检索了所发现出版物的参考文献目录,以查找相关的补充研究。出版物的纳入标准为英语、患者年龄≥18岁、发表年份大于1980年、原创研究、FHA诊断有效、经阴道超声诊断PCOM有效:FHA妇女的PCOM患病率从41.9%到46.7%不等,高于健康的非PCOS对照组。从理论上推测,高发病率可能是由于与普通人群一样的无声 PCOM 和已存在的多囊卵巢综合症混合造成的。在 FHA-PCOM 和 FHA-non-PCOM 患者之间发现了代谢和激素参数的一些差异。虽然两组患者都存在雌激素缺乏,但与 FHA 非 PCOM 患者相比,FHA-PCOM 患者的体重指数(BMI)较高,抗缪勒氏管激素(AMH)和睾酮水平较高,在 GnRH 测试过程中 LH 升高,性激素结合球蛋白(SHBG)水平较低。FHA-PCOM 与多囊卵巢综合征(PCOS),尤其是多囊卵巢综合征表型 D(PCOS、少排卵/无排卵但无雄激素过多症)之间的鉴别诊断具有挑战性。已经提出了一些参数,虽然并非绝对可靠,但很有帮助。它们包括导致 FHA 的典型原因(过度运动、能量不足和/或心理压力)、血清 LH、睾酮和 SHBG 水平以及孕激素挑战试验。至于 FHA-PCOM 是否会对患者的新陈代谢和心血管状况以及骨质造成不同的长期风险影响,目前尚不清楚。在治疗方面,有关 FHA-PCOM 与 FHA 非 PCOM 相比的数据很少。在治疗无排卵方面,使用脉冲性 GnRH 治疗似乎对两组患者都同样有效。与非 FHA-PCOM 患者类似,对于 FHA-PCOM 患者,脉冲性 GnRH 治疗比外源性促性腺激素更有效:更广泛的意义:患有 FHA-PCOM 的女性是 FHA 患者中的一个特殊亚群。在有关 FHA 和多囊卵巢综合症的临床指南中,应强调 FHA-PCOM 的诊断陷阱。在促性腺激素血清水平较低的情况下,近一半的 FHA 妇女卵泡过多(即 PCOM),这一事实表明,卵巢内部对卵泡生成的调节受个体差异的影响,其原因不明,可能是遗传因素,也可能是表观遗传因素。这一假设还需要进一步研究:不适用。
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来源期刊
Human Reproduction Update
Human Reproduction Update 医学-妇产科学
CiteScore
28.80
自引率
1.50%
发文量
38
期刊介绍: Human Reproduction Update is the leading journal in its field, boasting a Journal Impact FactorTM of 13.3 and ranked first in Obstetrics & Gynecology and Reproductive Biology (Source: Journal Citation ReportsTM from Clarivate, 2023). It specializes in publishing comprehensive and systematic review articles covering various aspects of human reproductive physiology and medicine. The journal prioritizes basic, transitional, and clinical topics related to reproduction, encompassing areas such as andrology, embryology, infertility, gynaecology, pregnancy, reproductive endocrinology, reproductive epidemiology, reproductive genetics, reproductive immunology, and reproductive oncology. Human Reproduction Update is published on behalf of the European Society of Human Reproduction and Embryology (ESHRE), maintaining the highest scientific and editorial standards.
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